Tremendous strides have been made over the last several years by DNA cloning and sequencing techniques in understanding the structures in DNA responsible for the expression of antibody molecules. Up to now all published analyses have been made using the mouse as the experimental system. In this proposed research we will extend the recombinant DNA approach to study immunoglobulin genes of man. This will provide comparative data for study of the evolution and function of these genes in mouse and man. Moreover, these studies will bear on some of the most prevalent forms of human B-cell leukemia. To approach this problem, lymphocytes from chronic lymphocytic leukemia patients will be used as a source of mRNA for cloning and tumor and germline DNA from these patients will be analyzed for deviations from the normal.